Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by lymphocytic infiltration ofthe exocrine glands that leads to severe oral and ocular dryness. SS is also a systemic disease that may include debilitating fatigue, lymphoma, neuropathies, pulmonary disease, and arthralgias. The etiology of SS is poorly understood, but clearly involves a complex genetic architecture influenced by environmental factors that lead to abnormal cellular and humoral immune responses. The difficulty in correctly diagnosing SS in addition to the scarcity of effective therapeutic options, often results in significant morbidity and irreversible damage to the exocrine glands. We propose to implement the resources and administrative structure to facilitate the translation of laboratory-based research in Sjogren's syndrome into relevant diagnostic, prognostic and therapeutic innovations in the field of autoimmune disease. The Oklahoma Sjogren's Syndrome Center of Research Translation (OSSCORT) will have the unique opportunity to bring together a strong core of well-funded laboratory-based scientists and clinical researchers at the Oklahoma Medical Research Foundation, with a multidisciplinary network of investigators committed to Sjogren's Syndrome Research from of the University of Oklahoma Health Sciences Center and multiple US and international sites. The OSSCORT will initially consist of three Projects and three Cores, and will in the successive years expand to include Pilot and Feasibility Projects, as well as an Enrichment Program. Project 1 will address the genetics of SS by applying state-of-the-art genome wide association and replication experiments, as well as genotypic delineation of sub-phenotypes. Project 2 will develop innovative approaches to reveal key features of T cell immune dysregulation in Sjogren's syndrome, and Project 3 will utilize a humanized mouse model of SS to test the hypothesis that B cells infiltrating the salivary glands of patients make autoantibodies that are in part responsible for the exocrine glandular dysfunction. The Cores that will assist and facilitate the OSSCORT are an Administrative Core, a Clinical Core and a Data Analysis and Bioinformatics Core led by experienced leaders in the field. RELEVANCE: We are witnesses of an increasing need to translate the relevant discoveries of laboratory-based research into clinically relevant results. The OSSCORT has the unique combination of clinical, scientific and administrative resources to improve understanding of the pathogenesis of SS. This will in turn create opportunities for new diagnostics, prognostic and therapeutic strategies that will benefit patients with this and other related diseases.